The incorporation of mevalonate into nonsaponifiable lipids by chick liver in vivo strongly increased between 1-18 days after hatching. Cholesterol feeding (2%) inhibited this. Synthesis of cholesterol was strongly inhibited, whereas the intermediates isolated by TLC accumulated. Most of the polar nonsaponifiable lipids that accumulated in liver 90 minutes after mevalonate administration to 18-day-old cholesterol-fed chicks were identified as lanosterol derivatives. 3-Hydroxy-3-methylglutaryl-CoA reductase activity, as well as acetate and mevalonate incorporation into nonsaponifiable lipids, was inhibited by the presence of these compounds. To our knowledge, this is the first report of such inhibition; this confirms the physiological function of polar steroids in the regulation of cholesterogenesis in vivo.
The in vivo incorporation of acetate into nonsaponifiable lipids was studied in different tissues from 14-day-old chick. Total nonsaponifiable lipids (nmol/30 min/g tissue) were mainly synthesized in testicles and liver. The in vivo CO2 production from acetate by 1-day-old chick did not exhibit diurnal variations. However, in 14-day-old chick, a maximal value was observed in the middle of the light period, while a minimal value was found 9 h after the start of the dark period. No significant diurnal differences were detected in the in vivo acetate incorporation into nonsaponifiable lipids by liver and duodenal mucosa from 1-day-old chick. Nevertheless, a clear diurnal rhythm was found in liver and duodenal mucosa from 14-day-old chick, but not in brain and kidney from animals of the same age. Distribution of radioactivity from (1-14C)acetate among the different constituents of the nonsaponifiable fraction has been also studied at 3-h intervals. Cholesterol was the major sterol formed from acetate by chick liver at any time of day. In duodenal mucosa and kidney, maximal values in the percentage of cholesterol synthesized were observed during the light period.
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